Garima Baral

Abstract Lung cancer is the leading cause of cancer-related deaths in the United States, and ~50% of these patients present with metastatic disease at diagnosis. Epithelial-to-Mesenchymal Transition (EMT) is an important initiating step in the metastatic cascade that allows cells to acquire the migratory and invasive phenotypes necessary for dissemination.

Abstract Oncogenic mutations in KRAS are present in ~95% of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) and are considered the initiating event of pancreatic intraepithelial neoplasia (PanIN) precursor lesions. While it is well established that KRAS mutations drive the activation of oncogenic kinase cascades during pancreatic oncogenesis, the effects of oncogenic KRAS signaling on regulation of phosphatases during this process is not fully appreciated.

Abstract Correctly identifying perturbed biological pathways is a critical step in uncovering basic disease mechanisms and developing much-needed therapeutic strategies. However, whether current tools are optimal for unbiased discovery of relevant pathways remains unclear. Here, we create “Benchmark” to critically evaluate existing tools and find that most function sub-optimally. We thus develop the “Pathway Ensemble Tool” (PET), which outperforms existing methods.